Table 2.

Microbiome-induced inflammation is associated with PDAC via multiple pathways with several proinflammatory factors.

Type	Microbiome	Functions in PDAC
Microbial dysbiosis	P. gingivalis	A critical role in initiating inflammation and escaping the immune response related to lipopolysaccharide (LPS) and toll-like receptors (TLRs)
	Fusobacterium	Fusobacterium could increase the production of ROS and inflammatory cytokines, and modulate the tumor immune microenvironment
	Helicobacter pylori	The Helicobacter pylori IgG level was higher in PDAC Helicobacter pylori may promote the development of PDAC by causing chronic mucosal inflammation as well as changes in cell proliferation and differentiation.
	Hepatotropic viruses HBV and HCV	HBsAg and HBcAg were found in the cytoplasm of pancreatic acinar cells Inflammation and modifying tissue viscoelasticity, DNA integration in infected cells that delay host immune system clearance of HBV/ HCV-containing cells Modulating the PI3K/AKT signaling pathway via the HBV/HCV protein
	Gammaproteobacteria Bifidobacterium pseudolongum	The pancreas is not sterile and has its own microbial environment which may affect the occurrence and development of PDAC. Gammaproteobacteria might modulate tumor sensitivity to gemcitabine.
	Other: Fungi and viruses	Oncogenic Kras-induced inflammation leads to fungal dysbiosis, which in turn promotes tumor progression via activation of the MBL-C3 cascade. The fungal microbiome drives a KrasG12D-MEK signaling pathway in PDAC cells that promotes the secretion of a pro-inflammatory cytokine, IL-33, which can subsequently hasten the spread of PDAC by secreting pro-tumorigenic cytokines such as IL-4, IL-5, and IL-13.
Microbial metabolites	lipopolysaccharide (LPS)	A Gram-negative bacterial cell wall component LPS can interact with several TLRs signaling pathways leading to T-cell anergy. LPS-TLR signaling can activate NF-κB, MAPK, the signal transducers and activators of STAT3 signaling pathway and trigger mutation of KRAS
	deoxycholic acid (DCA) and short-chain fatty acids (SCFAs)	They both promote intestinal tumorigenesis in conjunction with adenomatous polyposis coli (Apc) gene mutation Causing DNA damage, modulating the inflammatory cytokines and chemokines expressing in the PDAC TME via activation of Wnt signaling which is important for cell proliferation during tumorigenesis. DCA can activate the epidermal growth factor receptor (EGFR)